This renewal seeks support to continue to maintain, promote and facilitate the effective and timely usage of the advanced and developing techniques of computerized mass spectrometry for the express purpose of solving biochemical, biological and medical research problems involving questions of key scientific significance which may be addressed by obtaining new experimental structural insight and identification at the molecular level. The program will continue to make available to investigators (both scientists and clinicians) in virtually all biological and medical research fields, the state-of-the-art techniques in high performance mass spectrometry and the facility staff expertise which are both essential for the successful symbiotic application of such advanced methodology and instrumentation to their individual research problems. We will continue to foster purposefully the salient ingredients pertinent to presently successful facility operations including the requirements for: 1) structure elucidation for covalently modified biopolymers of all types - usually polar, polyfunctional and labile in nature; 2) studies on the qualitative and quantitative composition of complex mixtures of polar, labile substances isolated from biological materials. The corresponding salient features of our methodology arsenal includes the requirements for: 1) the complementary "soft ionization" sample ion sources; 2) the new highest sensitivity ion optical systems possessing state-of-the-art mass ranges (approximately 10,000-15,000 dalton); 3) new instrumental strategies for signal enhancement and elimination of chemical/matrix associated, etc. "noise"; and spectral accumulation methods; 4) relevant computer system support of instrumentation; and 5) essential isolation, degradation and chromatographic separation methodology for core and collaborative problem development. Specific problem areas of biomedical and clinical research importance include: the metabolism, conjugation and macro-molecular covalent binding of endogenous and xenobiotic substances, the molecular basis of toxicity, chemical and oncogenic carcinogenesis, nature of glycoconjugates in inter-molecular recognition (antigenic determinants, etc.), and genetic disorders, etc.